Optical particle analyzers are frequently used in pharmaceutical, environmental, life-science, and materials-science applications to measure particle dimensions and particle concentrations of samples including particles dispersed in a carrier. The validity of such measurements is dependent on the measurement accuracy and the detection sensitivity of the optical particle analyzer. Measurement accuracy is the ability of the optical particle analyzer to measure particle dimensions accurately. Detection sensitivity is the ability of the optical particle analyzer to measure particle concentrations accurately.
The detection sensitivity and the measurement accuracy of an optical particle analyzer are, typically, assessed using a particle standard. A conventional particle standard is a sample including particles of a predetermined particle dimension, within narrow predetermined limits, dispersed in a carrier at a predetermined particle concentration. In most instances, the carrier is a fluid, usually water, as described in U.S. Pat. No. 6,542,833 to Nygaard, issued on Apr. 1, 2003, and in U.S. Pat. No. 4,331,862 to Ryan, issued on May 25, 1982, for example; however, in some instances, the carrier is a solid plate, as described in U.S. Patent Application Publication No. 2006/0033909 to Bowers, et al., published on Feb. 16, 2006. The predetermined particle dimension and the predetermined particle concentration of the particle standard are, generally, matched to the particle dimension and the particle concentration, respectively, of a sample under study. Furthermore, a value of an optical property of the particles and/or a value of an optical property of the carrier may also be matched to those of the sample under study, as described in U.S. Pat. No. 6,521,729 to Zelmanovic, et al., issued on Feb. 18, 2003, and in U.S. Pat. No. 6,475,800 to Hazen, et al., issued on Nov. 5, 2002.
The particle dimension of the particle standard is measured with the optical particle analyzer, and the measured particle dimension is compared to the predetermined particle dimension to determine the measurement accuracy of the optical particle analyzer for that particle standard. Similarly, the particle concentration of the particle standard is measured with the optical particle analyzer, and the measured particle concentration is compared to the predetermined particle concentration to determine the detection sensitivity of the optical particle analyzer for that particle standard.
The measurement of particle dimensions and particle concentrations of samples including particles and a carrier having similar values of an optical property poses particular challenges. Examples of such samples include protein drug formulations and cell-culture samples. As the value of an optical property, such as refractive index or a transmission property, of the particles approaches that of the carrier, it becomes increasingly difficult for the optical particle analyzer to distinguish the particles from the carrier. As a result, the optical particle analyzer is susceptible to measurement errors. For example, if the contrast between the particles and the carrier is insufficient, the outer edges of the particles may effectively disappear to the detector of the optical particle analyzer, leading to a measured particle dimension that is smaller than the actual particle dimension. Furthermore, some particles may not be detected at all, leading to a measured particle concentration that is lower than the actual particle concentration.
Thus, it would be desirable to assess the measurement accuracy and the detection sensitivity of an optical particle analyzer for samples in which the particles and the carrier have similar values of an optical property. Such an assessment would permit minimum instrument specifications to be established, instrument performance to be compared, standardized, and verified, and advances in instrument technology to be quantified. Unfortunately, a set of particle standards necessary for such an assessment does not currently exist.
An object of the present invention is to provide a plurality of samples, each of which includes particles dispersed in a carrier, to be used as a set of particle standards for assessment of the measurement accuracy or the detection sensitivity of an optical particle analyzer as a value of an optical property of the particles approaches that of the carrier. The present invention also provides a method of using the plurality of samples for such an assessment.